The Role of Kif4A in Doxorubicin-Induced Apoptosis in Breast Cancer Cells

• DOI: 10.14348/molcells.2014.0210
• Publication Date: 2014-12-09T08:53:01Z
• Authors: Hui Wang; Changqing Lu; Qing Li; Jun Xie; Tongbing Chen; Yan Tan; Changping Wu; Jingting Jiang
• Keywords: 0301 basic medicine; Poly Adenosine Diphosphate Ribose; Antibiotics, Antineoplastic; Poly (ADP-Ribose) Polymerase-1; Kinesins; Apoptosis; Breast Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Article; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Doxorubicin; Cell Line, Tumor; Benzamides; MCF-7 Cells; Humans; Female; Poly(ADP-ribose) Polymerases; Cell Proliferation

This study was to investigate the mechanism and role of Kif4A in doxorubicin-induced apoptosis in breast cancer. Using two human breast cancer cell lines MCF-7 (with wild-type p53) and MDA-MB-231 (with mutant p53), we quantitated the expression levels of kinesin super-family protein 4A (Kif4A) and poly (ADP-ribose) Polymerase-1 (PARP-1) by Western blot after doxorubicin treatment and examined the apoptosis by flow cytometry after treatment with doxorubicin and PARP-1 inhibitor, 3-Aminobenzamide (3-ABA). Our results showed that doxorubicin treatment could induce the apoptosis of MCF-7 and MDA-MB-231 cells, the down-regulation of Kif4A and upregulation of poly(ADP-ribose) (PAR). The activity of PARP-1 or PARP-1 activation was significantly elevated by doxorubicin treatment in dose- and time-dependent manners (P < 0.05), while doxorubicin treatment only slightly elevated the level of cleaved fragments of PARP-1 (P > 0.05). We further demonstrated that overexpression of Kif4A could reduce the level of PAR and significantly increase apoptosis. The effect of doxorubicin on apoptosis was more profound in MCF-7 cells compared with MDA-MB-231 cells (P < 0.05). Taken together, our results suggest that the novel role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells is achieved by inhibiting the activity of PARP-1.